Method For Identifying And Using Compounds That Inactivate Hiv-1 And Other Retroviruses By Attacking Highly Conserved Zinc Fingers In The Viral Nucleocapsid Protein
Louis E. Henderson - Mt. Airy MD, US Larry O. Arthur - Walkersville MD, US William G. Rice - Frederick MD, US
Assignee:
The United States of America as represented by the Secretary of the Department of Health and Human Services - Washington DC
International Classification:
C12H 7/04 C12H 7/06 C07C 321/00 C07D 207/444
US Classification:
435236, 435238, 568 21, 568 25, 548548
Abstract:
The present invention provides several classes of compounds which can be used to inactivate retroviruses, such as HIV-1, by attacking the CCHC zinc fingers of the viral nucleocapsid protein and ejecting the zinc therefrom. In addition, kits for identifying compounds that can react with CCHC zinc fingers of the nucleocapsid proteins of a large number of different retroviruses have also been developed. The kits of the present invention describe a set of specific tests and reagents that can be used to screen and identify compounds based on their ability to react with and disrupt retroviral zinc fingers in the viral NC proteins and, in turn, inactivate the retrovirus of interest.
Hiv Nucleocapsid Protein Capture Assay And Method Of Use
Larry O. Arthur - Walkersville MD Louis E. Henderson - Mt. Airy MD
Assignee:
The United States of America as represented by the Secretary Department of Health & Human Services - Washington DC
International Classification:
C12Q 170
US Classification:
435 5
Abstract:
An antigen capture method, and an antigen capture assay diagnostic kit, for detecting the presence or concentration of HIV in a biological sample without interference from antigen-antibody immune complexes is provided. The lysate of a biological sample obtained from an animal is contacted with a detectable mount of an antibody specifically reactive with the nucleocapsid p7 antigen or an immunoreactive fragment of the p7 antigen for a time and under conditions sufficient for p7 antigen contained in the lysate to form a p7-antibody complex. The presence or concentration of this p7-antibody complex is determined to detect or quantitate the presence of HIV in the biological sample. Uses of this assay and method include detecting the presence of HIV infection in an infant born to an HIV-infected mother, monitoring the progression of HIV infection, and evaluating the effectiveness of an anti-HIV treatment administered to an animal, such as a human. Purified antibodies specifically reactive with an immunoreactive epitope specific to p7 or an immunoreactive fragment of p7 are also provided as well as an antigen capture method for detecting the presence of a lentivirus in a biological sample involving the nucleocapsid protein of the lentivirus.
Hiv Nucleocapsid Protein Capture Assay And Method Of Use
Larry O. Arthur - Walkersville MD Louis E. Henderson - Mt. Airy, both od MD
Assignee:
The Government of the United States of America, as Represented by the Secretary, DHHS - Rockville MD
International Classification:
C12Q 170
US Classification:
435 5
Abstract:
An antigen capture method, and an antigen capture assay diagnostic kit, for detecting the presence or concentration of HIV in a biological sample without interference from antigen-antibody immune complexes is provided. The lysate of a biological sample obtained from an animal is contacted with a detectable amount of an antibody specifically reactive with the nucleocapsid p7 antigen or an immunoreactive fragment of the p7 antigen for a time and under conditions sufficient for p7 antigen contained in the lysate to form a p7-antibody complex. The presence or concentration of this p7-antibody complex is determined to detect or quantitate the presence of HIV in the biological sample. Uses of this assay and method include detecting the presence of HIV infection in an infant born to an HIV-infected mother, monitoring the progression of HIV infection, and evaluating the effectiveness of an anti-HIV treatment administered to an animal, such as a human. Purified antibodies specifically reactive with an immunoreactive epitope specific to p7 or an immunoreactive fragment of p7 are also provided as well as an antigen capture method for detecting the presence of a lentivirus in a biological sample involving the nucleocapsid protein of the lentivirus.
Method For Identifying And Using Compounds That Inactivate Hiv-1 And Other Retroviruses By Attacking Highly Conserved Zinc Fingers In The Viral Nucleocapsid Protein
Louis E. Henderson - Mt. Airy MD Larry O. Arthur - Walkersville MD William G. Rice - Frederick MD Alan R. Rein - Takoma Park MD
Assignee:
The United States of America as represented by the Department of Health and Human Services - Washington DC
International Classification:
C12Q 170
US Classification:
435 5
Abstract:
The present invention provides several classes of compounds which can be used to inactivate retroviruses, such as HIV-1, by attacking the CCHC zinc fingers of the viral nucleocapsid protein and ejecting the zinc therefrom. In addition, kits for identifying compounds that can react with CCHC zinc fingers of the nucleocapsid proteins of a large number of different retroviruses have also been developed. The kits of the present invention describe a set of specific tests and reagents that can be used to screen and identify compounds based on their ability to react with and disrupt retroviral zinc fingers in the viral NC proteins and, in turn, inactivate the retrovirus of interest.
Design And Construction Of Non-Infectious Human Retroviral Mutants Deficient In Genomic Rna
Robert J. Gorelick - Braddock Heights MD Larry O. Arthur - Walkersville MD Alan Rein - Takoma Park MD Louis E. Henderson - Mount Airy MD Stephen Oroszlan - Potomac MD
Assignee:
United States of America - Washington DC
International Classification:
C12N 1300 C12P 2106 C07K 100 A61K 3921
US Classification:
4351723
Abstract:
The present invention defines a biological role for the following sequence of amino acids that is found in the nucleocapsid domain of the gag precursor polyproteins of all replication-competent retroviruses: -Cys-X-X-Cys-X-X-X-X-His-X-X-X-X-Cys- wherein X represents variable amino acids. The invariant residues constitute part of a vital protein structure, at least one of which are found in all retroviruses and which are involved in the selection and packaging of genomic viral RNA into infectious virus particles. Disruption of this structure leads to the formation of virus-like particles which appear to be structurally normal, but which do not contain the normal complement of viral RNA. Therefore, their infectivity is drastically reduced or completely eliminated. The infectivity of any retrovirus, including human retroviruses, and more particularly human immunodeficiency virus (HIV), can be drastically reduced or completely eliminated by generating mutants that lack some or all of the invariant residues required to form the structure.
Name / Title
Company / Classification
Phones & Addresses
Larry Arthur President
Saic Frederick Inc Noncommercial Research Organizations
Miller Dr Bldg 428, Frederick, MD 21701
Larry Arthur President
Saic Inc Commercial Economic, Sociological, and Educat...
Po Box B, Frederick, MD 21702 Website: saic.com
Larry Arthur Director
National Institutes of Health National Cancer Institute
92 Thomas Johnson Dr, Frederick, MD 21702
Larry Arthur Principal
Larry O Arthur Dr Medical Doctor's Office
10338 Harp Rd, Walkersville, MD 21793
Larry Arthur Branch Manager
Science Applications International Corporation Commercial Physical Research & Development
Po Box B, Frederick, MD 21702 Ft Detrick, Frederick, MD 21702 3018461086
Larry Arthur President
Saic-Frederick, Inc Noncommercial Research Organization · Research & Development in Biotechnology
School of Liberal Arts and Professional Studies, University of Pennsylvania Philadelphia, PA Jan 2012 to Aug 2012 Adjunct ProfessorWistar Institute, University of Pennsylvania Philadelphia, PA Oct 2009 to Jan 2012 Postdoctoral FellowHood College Frederick, MD Sep 2006 to Aug 2009 Adjunct ProfessorHood College Rockville, MD Sep 2006 to Jan 2008 Research ScientistUniversity of Maryland, University College
Sep 2004 to Jul 2006 Assistant Professor of Biology EuropeanUniversity of Maryland Medical School Baltimore, MD Dec 2003 to Sep 2004 Postdoctoral FellowUniversity of Maryland Medical School Baltimore, MD Sep 1997 to Dec 2003 Graduate Research Assistant Molecular and Cell Biology ProgramJohns Hopkins University School of Hygiene and Public Health Baltimore, MD Jul 1996 to Sep 1997 Laboratory Technician, Department of Molecular
Education:
University of Maryland Medical School Baltimore, MD 2003 Ph.D. in Molecular and Cell BiologyTowson University Towson, MD 1997 B.S. in Biology
Wistar Institute, University of Pennsylvania Philadelphia, PA Sep 2011 to Aug 2012 Adjunct ProfessorWistar Institute, University of Pennsylvania Philadelphia, PA Oct 2009 to Jan 2012 Postdoctoral FellowHood College Frederick, MD Sep 2006 to Aug 2009 Adjunct ProfessorHood College Rockville, MD Sep 2006 to Jan 2008 Research ScientistHood College Shaping, CN 2007 to 2008University of Maryland, University College
Sep 2004 to Jul 2006 Assistant Professor of Biology European traveling facultyUniversity of Maryland Medical School Baltimore, MD Dec 2003 to Sep 2004 Postdoctoral FellowUniversity of Maryland Medical School Baltimore, MD Sep 1997 to Dec 2003 Graduate Research Assistant Molecular and Cell Biology ProgramJohns Hopkins University School of Hygiene and Public Health Baltimore, MD Jul 1996 to Sep 1997 Laboratory Technician, Department of Molecular
Education:
University of Maryland Medical School Baltimore, MD 2003 B.S. in BiologyTowson University Towson, MD 1997
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